High-pressure liquid chromatographic--mass spectrometric determination of delta9-tetrahydrocannabinol in human plasma following marijuana smoking.

A method was developed for analyzing delta9-tetrahydrocannabinol (I), a psychotomimetic constituent found in marijuana smoke. The developed method utilizes a high-pressure liquid chromatographic (HPLC) gradient elution program to separate I from the other major cannabinoids in marijuana smoke. To achieve the sensitivity required to detect I in human plasma following marijuana smoking, a mass spectrometric quantification method was developed to analyze the HPLC eluant. To 1 ml of human plasma was added a known amount of internal standard, trideuterated I. This stable isotope provided a check on extraction efficiency, a marker for UV monitoring of the HPLC effluent and subsequent collection, and a convenient mass for mass spectrometric quantification. An ion-counting technique was used in conjunction with the peak matching accessory of the mass spectrometer to provide for a rapid comparison between molecular ions of I and the internal standard. The method was linear, accurate, and reproducible over the concentration range expected for I in plasma following marijuana smoking; 2.5 ng/ml was the lower practical limit of detection. Plasma from 11 male subjects was analyzed by the method at appropriate intervals up to 24 hr after the smoking of a marijuana cigarette containing 10.8 mg of I. Results demonstrated that levels of I could be determined accurately in the plasma of marijuana smokers in the 1-hr period following smoking.